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Record Information
Version2.0
Creation Date2009-07-30 17:59:13 UTC
Update Date2014-12-24 20:26:08 UTC
Accession NumberT3D3542
Identification
Common NameValaciclovir
ClassSmall Molecule
DescriptionValaciclovir (INN) or valacyclovir (USAN) is an antiviral drug used in the management of herpes simplex and herpes zoster (shingles). It is a prodrug, being converted in vivo to aciclovir. It is marketed by GlaxoSmithKline under the trade name Valtrex or Zelitrex. [Wikipedia]
Compound Type
  • Amide
  • Amine
  • Antiviral Agent
  • Drug
  • Ester
  • Ether
  • Metabolite
  • Organic Compound
  • Prodrug
  • Synthetic Compound
Chemical Structure
Thumb
Synonyms
Synonym
Bagovir
Cycloval
L-Valine ester with 9-((2-hydroxyethoxy)methyl)guanine
L-Valine, 2-((2-amino-1,6-dihydro-6-oxo-9H-purin-9-yl)methoxy)ethyl ester
Mitanga
Ovalac
Pervioral
Revira
Vacyless
Vadiral
Valaciclovirum
Valacyclover Hydrochloric
Valacyclovir
Valdacir
Valotix
Valtrex
Valvir
Valztrex
Viramixal
Viropel
Vociflon
Zelitrex
Zelivire
Chemical FormulaC13H20N6O4
Average Molecular Mass324.336 g/mol
Monoisotopic Mass324.155 g/mol
CAS Registry Number124832-26-4
IUPAC Name2-[(2-amino-6-oxo-6,9-dihydro-3H-purin-9-yl)methoxy]ethyl (2S)-2-amino-3-methylbutanoate
Traditional Namevaltrex
SMILES[H][C@](N)(C(C)C)C(=O)OCCOCN1C=NC2=C1NC(=N)N=C2O
InChI IdentifierInChI=1S/C13H20N6O4/c1-7(2)8(14)12(21)23-4-3-22-6-19-5-16-9-10(19)17-13(15)18-11(9)20/h5,7-8H,3-4,6,14H2,1-2H3,(H3,15,17,18,20)/t8-/m0/s1
InChI KeyInChIKey=HDOVUKNUBWVHOX-QMMMGPOBSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as alpha amino acid esters. These are ester derivatives of alpha amino acids.
KingdomOrganic compounds
Super ClassOrganic acids and derivatives
ClassCarboxylic acids and derivatives
Sub ClassAmino acids, peptides, and analogues
Direct ParentAlpha amino acid esters
Alternative Parents
Substituents
  • Alpha-amino acid ester
  • Valine or derivatives
  • 6-oxopurine
  • Hypoxanthine
  • Imidazopyrimidine
  • Purine
  • Aminopyrimidine
  • Pyrimidone
  • Fatty acid ester
  • N-substituted imidazole
  • Pyrimidine
  • Fatty acyl
  • Azole
  • Heteroaromatic compound
  • Vinylogous amide
  • Imidazole
  • Carboxylic acid ester
  • Azacycle
  • Organoheterocyclic compound
  • Monocarboxylic acid or derivatives
  • Organooxygen compound
  • Primary amine
  • Organic oxygen compound
  • Organic nitrogen compound
  • Hydrocarbon derivative
  • Carbonyl group
  • Organic oxide
  • Organopnictogen compound
  • Primary aliphatic amine
  • Amine
  • Organonitrogen compound
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Cytoplasm
  • Extracellular
  • Membrane
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
ApplicationsNot Available
Biological RolesNot Available
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceThe blue, film-coated caplets are printed with edible white ink.
Experimental Properties
PropertyValue
Melting PointNot Available
Boiling PointNot Available
Solubility3.55e+00 g/L
LogP-0.3
Predicted Properties
PropertyValueSource
Water Solubility3.55 g/LALOGPS
logP-0.84ALOGPS
logP-0.45ChemAxon
logS-2ALOGPS
pKa (Strongest Acidic)8.1ChemAxon
pKa (Strongest Basic)7.36ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count8ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area146.85 ŲChemAxon
Rotatable Bond Count8ChemAxon
Refractivity80.63 m³·mol⁻¹ChemAxon
Polarizability31.96 ųChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyView
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-00di-9210000000-51af1895b69904867582JSpectraViewer
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-0udi-1910000000-3db14f76ba496cea0d81JSpectraViewer | MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0udi-1913000000-e8d1da3daee2d7637783JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0udi-2900000000-90825e6bac8b121f346eJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0zg0-2900000000-9ced6b2b253471425de0JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-00xs-5913000000-05fdd28b28d4365d3f85JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-106s-5922000000-36d450a0ce5422cc73d6JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0pbc-5900000000-8eaf432e968b85e4cb9aJSpectraViewer
Toxicity Profile
Route of ExposureAfter oral administration, valaciclovir hydrochloride is rapidly absorbed from the gastrointestinal tract. The absolute bioavailability of acyclovir after administration of valaciclovir is 54.5% ± 9.1%.
Mechanism of ToxicityValaciclovir is phosphorylated by viral thymidine kinase to acyclovir triphosphate (the active metabolite) which then inhibits herpes viral DNA replication by competitive inhibition of viral DNA polymerase, and by incorporation into and termination of the growing viral DNA chain. When used as a substrate for viral DNA polymerase, acyclovir triphosphate competitively inhibits dATP leading to the formation of 'faulty' DNA. This is where acyclovir triphosphate is incorporated into the DNA strand replacing many of the adenosine bases. This results in the prevention of DNA synthesis, as phosphodiester bridges can longer to be built, destabilizing the strand.
MetabolismValaciclovir is rapidly and almost entirely (~99%) converted to the active compound, acyclovir, and L-valine by first-pass intestinal and hepatic metabolism by enzymatic hydrolysis. Neither valaciclovir nor acyclovir is metabolized by cytochrome P450 enzymes. Acyclovir is converted to a small extent to inactive metabolites by aldehyde oxidase and by alcohol and aldehyde dehydrogenase. Plasma concentrations of unconverted valacyclovir are low and transient, generally becoming non-quantifiable by 3 hours after administration. Peak plasma valacyclovir concentrations are generally less than 0.5 mcg/mL at all doses. After single-dose administration of 1 gram of VALTREX, average plasma valacyclovir concentrations observed were 0.5, 0.4, and 0.8 mcg/mL in patients with hepatic dysfunction, renal insufficiency, and in healthy volunteers who received concomitant cimetidine and probenecid, respectively. Route of Elimination: Acyclovir accounted for 89% of the radioactivity excreted in the urine. Half Life: 2.5-3.3 hours
Toxicity ValuesNot Available
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesFor the treatment or suppression of cold sores (herpes labialis), herpes zoster (shingles), genital herpes in immunocompetent individuals, and recurrent genital herpes in HIV-infected individuals. Cold Sores (Herpes Labialis): VALTREX is indicated for treatment of cold sores (herpes labialis). The efficacy of VALTREX initiated after the development of clinical signs of a cold sore (e.g., papule, vesicle, or ulcer) has not been established. Genital Herpes: Initial Episode: VALTREX is indicated for treatment of the initial episode of genital herpes in immunocompetent adults. The efficacy of treatment with VALTREX when initiated more than 72 hours after the onset of signs and symptoms has not been established.
Minimum Risk LevelNot Available
Health EffectsGeneral: Facial edema, hypertension, tachycardia. Allergic:Acute hypersensitivity reactions including anaphylaxis, angioedema, dyspnea, pruritus, rash, and urticaria. CNS Symptoms: Aggressive behavior; agitation; ataxia; coma; confusion; decreased consciousness; dysarthria; encephalopathy; mania; and psychosis, including auditory and visual hallucinations, seizures, tremors. Eye: Visual abnormalities. Gastrointestinal: Diarrhea. Hepatobiliary Tract and Pancreas: Liver enzyme abnormalities, hepatitis. Renal: Renal failure, renal pain (may be associated with renal failure). Hematologic: Thrombocytopenia, aplastic anemia, leukocytoclastic vasculitis, TTP/HUS. Skin: Erythema multiforme, rashes including photosensitivity, alopecia.
SymptomsAdverse effects of overexposure might include headache and nausea.
TreatmentIn the event of acute renal failure and anuria, the patient may benefit from hemodialysis until renal function is restored. (5)
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB00577
HMDB IDHMDB14716
PubChem Compound ID60773
ChEMBL IDCHEMBL1349
ChemSpider ID54770
KEGG IDC07184
UniProt IDNot Available
OMIM ID
ChEBI ID35854
BioCyc IDNot Available
CTD IDNot Available
Stitch IDValaciclovir
PDB IDTXC
ACToR IDNot Available
Wikipedia LinkValaciclovir
References
Synthesis Reference

Marina Etinger, “Synthesis and purification of valacyclovir.” U.S. Patent US20030153757, issued August 14, 2003.

MSDSLink
General References
  1. O'Brien JJ, Campoli-Richards DM: Acyclovir. An updated review of its antiviral activity, pharmacokinetic properties and therapeutic efficacy. Drugs. 1989 Mar;37(3):233-309. [2653790 ]
  2. Umapathy NS, Ganapathy V, Ganapathy ME: Transport of amino acid esters and the amino-acid-based prodrug valganciclovir by the amino acid transporter ATB(0,+). Pharm Res. 2004 Jul;21(7):1303-10. [15290873 ]
  3. Drugs.com [Link]
  4. RxList: The Internet Drug Index (2009). [Link]
  5. RxList: The Internet Drug Index (2009). [Link]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available